HPSC based therapy for HIV disease using RNAi to CCR5.

The need for novel approaches to the treatment of HIV infection has never been greater, because new infections continue to occur at undiminished rates, in California and across the nation, despite decades of prevention efforts. Moreover, the number of people living with HIV is rising steadily, thanks to improved management of HIV infection. As a result, California, which ranks second in the nation in diagnosed cases of HIV infection, behind only New York, has identified 67,500 men, women, and children who carry the virus. (Estimates of the number of Californians who are infected but have yet to be diagnosed range as high as 33,513.) Not all of the state’s HIV-positive residents are currently on therapy, but eventually virtually all of them will be—and many of them will receive their drugs through government-supported programs. In addition, the longer these infected individuals live, the more likely they are to avail themselves of a range of support services that the state pays for. The drugs themselves, which are routinely administered in combination, are initially effective in suppressing viral replication in infected individuals, but their potency diminishes over time, even as the toxic effects of therapy accumulate. California, which is supporting the nation’s second-highest case-load of HIV-positive individuals, can expect to see that number grow at a rate of 5,000-7,000 a year for the foreseeable future. The cost of providing life-sustaining medications and social services to this burgeoning population will also continue to rise, not arithmetically but exponentially—because as increasing numbers of infected individuals fail standard drug regimens, it will be necessary to shift them to newer, more expensive treatments, and as the side effects of therapy become more manifest, it will be necessary to prescribe drugs to combat those toxicities, adding to the overall drug burden for patients and the overall cost of drug therapy for the state. In such circumstances, the prospect of stem-cell based therapy that will require “only a single treatment” is especially compelling. In theory, RNA interference might effectively cure individuals infected with HIV, by blocking the ports through which the virus enters CD4 cells and destroys the body’s immune system. And even if RNA interference proves only partially effective in blocking viral entry, it could significantly suppress viremia while sparing patients the toxicities associated with drug therapy. This would be a boon to infected individuals, but it would also be a benefit to uninfected Californians, because reductions in viremia in infected individuals translate into a reduction in the community burden of HIV infection—and that, in turn, reduces the overall rate of new infections statewide.